Management of DE With IPL in Combination With DQS

Dry Eye Clinical Trial

Official title:

Management of Dry Eye With Intense Pulsed Light in Combination With Diquafosol

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05694026
• Other study ID #: IPLDQS2023
• Status: Completed
• Phase: N/A
• Start date: March 1, 2023
• Est. completion date: July 1, 2023

Study information

• Verified date: July 2023
• Source: He Eye Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Intense pulsed light (IPL) has been reported to improve signs and symptoms of dry eye (DE). Additionally, meibomian gland secretion of lipids has been observed to improve through the use of IPL. Diquafosol ophthalmic solution (DQS) stimulates P2Y2 receptors on the ocular surface, which enhances mucin secretion from goblet cells. Therefore, tear film stability and hydration of the ocular surface can be achieved independent from lacrimal glands function. The purpose of this prospective study was to evaluate and compare the effects of IPL (IPL group), DQS (DQS group) and IPL in combination with DQS (IPL+ group) in participants with persistent DE. Tear film lipid layer (TFLL), non-invasive breakup time (NITBUT), tear meniscus height (TMH), corneoconjunctival staining score (CS), meibum gland (MG) function, conjunctival hyperemia (RS score), ocular surface disease index (OSDI) will be assessed and compared at baseline, day-14, and day-28.

Description:

Evaporative dry eye (EDE) has been reported to be the most prevalent form of dry eye disease (DED), which is primarily caused by meibomian gland hypofunction or meibomian gland dysfunction (MGD). MGD is defined as ''a chronic, diffuse anomaly of the meibomian glands, often characterized by terminal duct blockage and/or qualitative/quantitative alterations in glandular secretion'' by the International Workshop on MGD.These glands are modified sebaceous glands that release meibum directly onto the ocular surface. Signs and symptoms of EDE and MGD can be addressed by improving the quality and quantity of meibum secretion.

Intense pulsed light (IPL) is widely used to treat dermatological conditions, and its noncoherent polychromatic light source with wide wavelength range of 500-1200 nm has been reported to stimulate facial sebaceous glands. The photothermal effect of IPL is postulated to relieve inflammation by removing aberrant surface microvasculature and enhances meibomian gland function. Furthermore, an increase in fibroblast proliferation, collagen formation and local blood flow has been associated with the application of IPL on the skin. Several studies have documented the benefits of IPL in alleviating signs and symptoms of DED on the periocular skin.

Diquafosol ophthalmic solution (DQS) is a dinucleotide polyphosphate which a purinoceptor agonist, when administered to the ocular surface, it binds to P2Y2 receptors and stimulates mucin and tear secretion. The corneal epithelium, conjunctival epithelium, lacrimal gland ductal epithelium, meibomian gland sebaceous cells, and meibomian gland ductal cells all express the P2Y2 receptor. Subsequently, enhanced secretion of mucin and tear secretion due to DQS ophthalmic solution leads to stabilization of the tear film, minimizes tear evaporation, and reduces mechanical friction thereby protecting the corneal epithelium.

The purpose of this study is to assess the management of DE by combining IPL and DQS eye drops.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 360
• Est. completion date: July 1, 2023
• Est. primary completion date: July 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Age =18 years

• Consenting participants

• Able and willing to comply with the treatment/follow-up schedule

• Bilateral signs and symptoms of dry eye disease: (i) Ocular Surface Disease Index (OSDI) questionnaire =13, (ii) Non-invasive tear break-up (NITBUT) = 5 seconds, (iii) conjunctival staining score (CS) =3 points. The presence of two or more criteria was used to establish a positive DE diagnosis based on the 2016 Asia Dry Eye Society criteria

Exclusion Criteria:

• A recent history (past 30 days) of topical ophthalmic medication use, including antibiotics, steroids, non-steroidal anti-inflammatory drugs, or required the chronic use of topical ophthalmic medications.

• Eyelids or intraocular tumors.

• Active allergy or infection, or inflammatory disease may prevent the subjects from completing the study at the ocular surface.

• Any structural changes in the lacrimal passage

• Glaucoma

• Diabetes or other systemic, dermatologic, or neurologic diseases that affect the health of the ocular surface.

• Use of any systemic anti-inflammatory drugs or medication that may interfere with tear production, such as antianxiety, anti-depressive, and antihistamine medications, within three months.

• Pregnancy or breastfeeding

• Contact lenses wearers.

Related Conditions & MeSH terms

• Dry Eye
• Dry Eye Syndromes
• Keratoconjunctivitis Sicca

Intervention

Device:
• Intense pulsed light
IPL treatment intensity was chosen based on the Fitzpatrick scale as follows: Fitzpatrick scale I, II, III, 10-15 J/cm2 with a 570-nm filter.

Drug:
• Diquafosol tetrasodium
3% Diquafosol tetrasodium eye drops will be used to assess its usefulness in dry eye signs and symptoms

Locations

Country	Name	City	State
China	He Eye Hospital	Shenyang	Liaoning

Sponsors (1)

Lead Sponsor	Collaborator
He Eye Hospital

Country where clinical trial is conducted

China, 

References & Publications (18)

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Chen Y, Li J, Wu Y, Lin X, Deng X, Yun-E Z. Comparative Evaluation in Intense Pulsed Light Therapy Combined with or without Meibomian Gland Expression for the Treatment of Meibomian Gland Dysfunction. Curr Eye Res. 2021 Aug;46(8):1125-1131. doi: 10.1080/0 — View Citation

Chhadva P, Goldhardt R, Galor A. Meibomian Gland Disease: The Role of Gland Dysfunction in Dry Eye Disease. Ophthalmology. 2017 Nov;124(11S):S20-S26. doi: 10.1016/j.ophtha.2017.05.031. — View Citation

Cowlen MS, Zhang VZ, Warnock L, Moyer CF, Peterson WM, Yerxa BR. Localization of ocular P2Y2 receptor gene expression by in situ hybridization. Exp Eye Res. 2003 Jul;77(1):77-84. doi: 10.1016/s0014-4835(03)00068-x. — View Citation

Craig JP, Nichols KK, Akpek EK, Caffery B, Dua HS, Joo CK, Liu Z, Nelson JD, Nichols JJ, Tsubota K, Stapleton F. TFOS DEWS II Definition and Classification Report. Ocul Surf. 2017 Jul;15(3):276-283. doi: 10.1016/j.jtos.2017.05.008. Epub 2017 Jul 20. — View Citation

Dota A, Sakamoto A, Nagano T, Murakami T, Matsugi T. Effect of Diquafosol Ophthalmic Solution on Airflow-Induced Ocular Surface Disorder in Diabetic Rats. Clin Ophthalmol. 2020 Apr 1;14:1019-1024. doi: 10.2147/OPTH.S242764. eCollection 2020. — View Citation

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Jeng SF, Chen JA, Chang LR, Chen CC, Shih HS, Chou TM, Chen HF, Feng GM, Yang CH. Beneficial Effect of Intense Pulsed Light on the Wound Healing in Diabetic Rats. Lasers Surg Med. 2020 Jul;52(6):530-536. doi: 10.1002/lsm.23183. Epub 2019 Nov 24. — View Citation

Jumblatt JE, Jumblatt MM. Regulation of ocular mucin secretion by P2Y2 nucleotide receptors in rabbit and human conjunctiva. Exp Eye Res. 1998 Sep;67(3):341-6. doi: 10.1006/exer.1998.0520. — View Citation

Kulkarni AA, Trousdale MD, Stevenson D, Gukasyan HJ, Shiue MH, Kim KJ, Read RW, Lee VH. Nucleotide-induced restoration of conjunctival chloride and fluid secretion in adenovirus type 5-infected pigmented rabbit eyes. J Pharmacol Exp Ther. 2003 Jun;305(3): — View Citation

Liu R, Rong B, Tu P, Tang Y, Song W, Toyos R, Toyos M, Yan X. Analysis of Cytokine Levels in Tears and Clinical Correlations After Intense Pulsed Light Treating Meibomian Gland Dysfunction. Am J Ophthalmol. 2017 Nov;183:81-90. doi: 10.1016/j.ajo.2017.08.0 — View Citation

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* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Non-invasive tear break-up time (NIBUT)	Non-invasive initial tear film breaking time will be assessed using the Keratograph 5M (Oculus, Germany) topographer. Three sequentially readings will be captured, and the median value will be included in the final analysis. The median value will be recorded.; Changes at day-14 and day-28 will be compare with baseline measurements.; Comparison between groups at baseline, day-14 and day-28 will also be examined.	Day-0 (baseline), day-14 and day-28
Primary	Ocular Surface Disease Index (OSDI)	OSDI, which is a questionnaire consisting of 12 questions for evaluating the effects of dry eye syndrome on vision, ocular symptoms and any condition associated with DED. The patient will answer each question on a scale ranging from 0 to 4, with 0 indicating 'none of the time' and 4 indicating 'all of the time'. If a certain question is deemed irrelevant, it will be marked as 'not applicable (N/A)' and excluded from the analysis. The OSDI total score is calculated according to the following formula. The scale ranges from 0 to 100, with higher scores representing more severe cases of dry eye syndrome.; Changes at day-14 and day-28 will be compare with baseline measurements.; Comparison between groups at baseline, day-14 and day-28 will also be examined	Day-0 (baseline), day-14 and day-28
Secondary	Fluorescein and lissamine conjunctival and cornea staining (CFS)	Fluorescein and lissamine staining of the ocular surface will be divided into three zones comprising nasal conjunctival, corneal, and temporal conjunctival areas. The staining score ranged from 0 to 3 for each zone, yielding a total score of 0-9 for the ocular surface.; Changes at day-14 and day-28 will be compare with baseline measurements.; Comparison between groups at baseline, day-14 and day-28 will also be examined.	Day-0 (baseline), day-14 and day-28
Secondary	Meibomian gland function and secretion quality	Meibum quality will be assessed under a slit-lamp: Five meibomian gland in the middle parts of the eyelid will be assessed using a scale of 0 to 3 for each gland (0 represented clear meibum; 1 represented cloudy meibum; 2 represented cloudy and granular meibum; and 3 represented thick, toothpaste like consistency meibum); Changes at day-14 and day-28 will be compare with baseline measurements.; Comparison between groups at baseline, day-14 and day-28 will also be examined.	Day-0 (baseline), day-14 and day-28
Secondary	Tear Film Lipid Layer Score (TFLL)	Tear Film Lipid Layer interferometry will be assessed using DR-1 (Kowa, Nagoya, Japan). The results will be graded as follows: grade 1, somewhat gray color, uniform distribution; grade 2, somewhat gray color, nonuniform distribution; grade 3, a few colors, nonuniform distribution; grade 4, many colors, nonuniform distribution; grade 5, corneal surface partially exposed.; Changes at day-14 and day-28 will be compare with baseline measurements.; Comparison between groups at baseline, day-14 and day-28 will also be examined.	Day-0 (baseline), day-14 and day-28
Secondary	Tear meniscus height (TMH)	Non-invasive first tear film breakup time using the Keratograph 5M (Oculus, Germany) topographer will be measured three times consecutively and the median value was recorded.; Changes at day-14 and day-28 will be compare with baseline measurements.; Comparison between groups at baseline, day-14 and day-28 will also be examined.	Day-0 (baseline), day-14 and day-28
Secondary	Conjunctival hyperemia (RS score)	Conjunctival hyperemia (RS score) will be assessed by Keratograph image (Oculus, Germany) of 1156*873 pixels, redness score (RS) (accurate to 0.1 U) was displayed on the computer screen that ranged from 0.0 (normal) to 4.0 (severe).; Changes at day-14 and day-28 will be compare with baseline measurements.; Comparison between groups at baseline, day-14 and day-28 will also be examined.	Day-0 (baseline), day-14 and day-28